We are studying the structures of carbohydrates on glycoproteins with a goal of understanding the relationships between protein structure and carbohydrate structure. Our systems include normal and cancer cells. Results from studies of fibroblasts and their malignant transformants indicate that changes in carbohydrate heterogeneity accompany cancer. We are attempting detailed studies on the relationship between proteins and carbohydrates by using myeloma and lymphoma cell lines producing IgM either as a cell membrane component or in soluble form. Our studies provide direct information on the relationship of protein structure to carbohydrate structure and how these change for membrane and soluble components. We are also using mutant cell lines which synthesize altered immunoglobulins to test our hypotheses about specific protein determinants for carbohydrate structures. Finally, we are comparing rates of synthesis and subcellular pathways for membrane-bound and secreted glycoproteins. Our data show that the pathway for membrane-bound IgM is significantly different than for soluble IgM. The pathway appears to be an important determinant for the structure of oligosaccharide side chains on IgM.